Data-driven unbiased curation of the TP53 tumor suppressor gene mutation database and validation by ultradeep sequencing of human tumors. - Sorbonne Université Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2012

Data-driven unbiased curation of the TP53 tumor suppressor gene mutation database and validation by ultradeep sequencing of human tumors.

Karolina Edlund
  • Function : Author
Ola Larsson
  • Function : Author
Ignas Bunikis
  • Function : Author
Magnus Sundström
  • Function : Author
Patrick Micke
  • Function : Author
Johan Botling
  • Function : Author

Abstract

Cancer mutation databases are expected to play central roles in personalized medicine by providing targets for drug development and biomarkers to tailor treatments to each patient. The accuracy of reported mutations is a critical issue that is commonly overlooked, which leads to mutation databases that include a sizable number of spurious mutations, either sequencing errors or passenger mutations. Here we report an analysis of the latest version of the TP53 mutation database, including 34,453 mutations. By using several data-driven methods on multiple independent quality criteria, we obtained a quality score for each report contributing to the database. This score can now be used to filter for high-confidence mutations and reports within the database. Sequencing the entire TP53 gene from various types of cancer using next-generation sequencing with ultradeep coverage validated our approach for curation. In summary, 9.7% of all collected studies, mostly comprising numerous tumors with multiple infrequent TP53 mutations, should be excluded when analyzing TP53 mutations. Thus, by combining statistical and experimental analyses, we provide a curated mutation database for TP53 mutations and a framework for mutation database analysis.

Domains

Cancer

Dates and versions

hal-01188067 , version 1 (28-08-2015)

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Cite

Karolina Edlund, Ola Larsson, Adam Ameur, Ignas Bunikis, Ulf Gyllensten, et al.. Data-driven unbiased curation of the TP53 tumor suppressor gene mutation database and validation by ultradeep sequencing of human tumors.. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109 (24), pp.9551-6. ⟨hal-01188067⟩
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